WO2011021492A1 - Process for production of formyl-substituted aromatic compounds - Google Patents
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Abstract
A process for the production of formyl-substituted aromatic compounds which comprises hydrolyzing a dihalomethyl -substituted aromatic compound represented by general formula (1) into the corresponding formyl-substituted aromatic compound in the presence of an iron salt, wherein an aldehyde and an iron salt are dissolved in the dihalomethyl-substituted aromatic compound prior to the occurrence of hydrolysis, and after the resulting reaction system reaches a reaction temperature sufficient to cause the hydrolysis, water is added to the reaction system at a rate that not exceeds the rate of consumption of water. In general formula (1), Ar is an aromatic ring; X is a halogen atom; Rs are each independently a monovalent organic group; and l is an integer of 1 to 3, m is an integer of 1 to 5, and n is an integer of 0 to 5, with l, m and n satisfying the relationship: 1 ≤ l + m + n ≤ 6. By employing this process, the dihalomethyl group of a dihalomethyl-substituted aromatic compound having a trifluoromethyl group as another substituent can by hydrolyzed in a short time.
Description
本発明は、染料、香料、医薬、農薬、その他の有機化合物の合成原料として有用なトリフルオロメチル基を有するホルミル基置換芳香族化合物（「芳香族アルデヒド」ということがある。)を製造する方法に関し、更に詳しくは環水素原子がトリフルオロメチル基で置換されたジハロメチル基置換芳香族化合物を加水分解して対応する芳香族アルデヒドを製造する方法に関する。
The present invention is a method for producing a formyl group-substituted aromatic compound having a trifluoromethyl group (sometimes referred to as “aromatic aldehyde”) useful as a raw material for synthesizing dyes, fragrances, medicines, agricultural chemicals and other organic compounds. More particularly, the present invention relates to a method for producing a corresponding aromatic aldehyde by hydrolyzing a dihalomethyl group-substituted aromatic compound in which a ring hydrogen atom is substituted with a trifluoromethyl group.
一般に、ジハロメチル基置換芳香族化合物であるベンザルクロライド類は単に水と混合して加熱するだけではベンズアルデヒド類への加水分解速度が遅いため、従来から種々の触媒を用いてベンザルクロライド類を加水分解するベンズアルデヒド類の製造方法が知られている。
In general, benzal chlorides, which are dihalomethyl group-substituted aromatic compounds, are slow to hydrolyze into benzaldehydes simply by mixing with water and heating. Therefore, benzal chlorides are conventionally hydrolyzed using various catalysts. Methods for producing benzaldehydes that decompose are known.
例えば、（１）酸又はアルカリ水溶液を用いてベンザルクロライド類を加水分解し、ベンズアルデヒド類を製造する方法（非特許文献１、２）、（２）塩化第一銅又は塩化第二銅の存在下、ベンザルクロライド類を加水分解し、ベンズアルデヒドを製造する方法（特許文献１、特許文献２）、（３）ベンザルクロライド類に鉄塩の水溶液を添加し、加水分解してベンズアルデヒド類を製造する方法（特許文献３）、（４）無水塩化亜鉛の存在下、ベンザルクロライド類を加水分解し、ベンズアルデヒド類を製造する方法（特許文献４）、（５）酸化亜鉛の存在下、べンザルクロライド類を加水分解し、ベンズアルデヒド類を製造する方法（特許文献５）、等の方法がある。
For example, (1) A method for producing benzaldehydes by hydrolyzing benzal chlorides using an acid or alkaline aqueous solution (Non-Patent Documents 1 and 2), (2) Presence of cuprous chloride or cupric chloride Below, benzal chlorides are hydrolyzed to produce benzaldehyde (Patent Document 1, Patent Document 2), (3) An aqueous solution of iron salt is added to benzal chlorides and hydrolyzed to produce benzaldehydes (Patent Document 3), (4) A method of hydrolyzing benzal chlorides in the presence of anhydrous zinc chloride to produce benzaldehydes (Patent Document 4), (5) In the presence of zinc oxide, There exist methods, such as the method (patent document 5) etc. which hydrolyze a salchloride and manufacture benzaldehyde.
これらの文献においては、芳香環上にトリフルオロメチル基が置換していない基質が取り上げられており、（３）の方法では、２－クロロベンザルクロリド５８．５gを約１０分の反応時間で加水分解し、９６．７％の収率で２－クロロベンズアルデヒドを得ている。
In these documents, a substrate in which the trifluoromethyl group is not substituted on the aromatic ring is taken up. In the method (3), 58.5 g of 2-chlorobenzal chloride is added in a reaction time of about 10 minutes. Hydrolysis yields 2-chlorobenzaldehyde in 96.7% yield.
また、ベンゼン環上の水素原子がトリフルオロメチル基で置換したベンザルクロライドの加水分解としては、液相反応では（６）８０％以上の硫酸による加水分解方法（特許文献６）や（７）塩化第二鉄触媒を用いた加水分解反応（特許文献７）が知られ、気相反応では（８）硫酸を担持した触媒（特許文献８）や金属塩化物や金属硫酸塩を活性炭に担持した触媒（特許文献９）を用いた加水分解方法が知られている。（６）の方法では、廃硫酸の処理の問題、気相反応では比較的高温であるため装置の耐食性、エネルギーコストなどに問題がある。さらに、（７）の塩化第二鉄触媒を用いた場合、２－トリフルオロメチル－５－フルオロメチルベンザルクロリドの加水分解に約３０時間の反応時間を要している。
As the hydrolysis of benzal chloride in which a hydrogen atom on the benzene ring is substituted with a trifluoromethyl group, in a liquid phase reaction, (6) hydrolysis method using 80% or more sulfuric acid (Patent Document 6) and (7) Hydrolysis reaction using ferric chloride catalyst (Patent Document 7) is known. In the gas phase reaction, (8) a catalyst supporting sulfuric acid (Patent Document 8) and metal chloride or metal sulfate supported on activated carbon. A hydrolysis method using a catalyst (Patent Document 9) is known. In the method (6), there are problems in the treatment of waste sulfuric acid, and in the gas phase reaction, since the temperature is relatively high, there are problems in the corrosion resistance of the apparatus, energy cost, and the like. Further, when the ferric chloride catalyst (7) is used, the reaction time of about 30 hours is required for hydrolysis of 2-trifluoromethyl-5-fluoromethylbenzal chloride.
本発明は、トリフルオロメチル基が置換したジハロメチル基置換芳香族化合物のジハロメチル基を短時間で加水分解して対応する芳香族アルデヒドを製造する方法を提供することを目的とする。
An object of the present invention is to provide a method for producing a corresponding aromatic aldehyde by hydrolyzing a dihalomethyl group of a dihalomethyl group-substituted aromatic compound substituted with a trifluoromethyl group in a short time.
本発明者らは、トリフルオロメチル基が置換したジハロメチル基置換芳香族化合物のジハロメチル基を鉄塩を触媒して加水分解する方法について検討したところ、原料のトリフルオロメチル基が置換したジハロメチル基置換芳香族化合物中に予めアルデヒド化合物と鉄塩を併せ存在させておくことで、目的とする芳香族アルデヒドの選択率が高くかつ著しく短時間で反応が完結することを見出し、本発明を完成させた。
The present inventors examined a method for hydrolyzing a dihalomethyl group of a dihalomethyl group-substituted aromatic compound substituted with a trifluoromethyl group by catalyzing an iron salt. By preliminarily presenting an aldehyde compound and an iron salt in the aromatic compound, it was found that the selectivity of the target aromatic aldehyde was high and the reaction was completed in a very short time, and the present invention was completed. .
芳香環に置換するトリフルオロメチル基は強力な電子吸引基であるためにトリフルオロメチル基が置換したジハロメチル基置換芳香族化合物のジハロメチル基の加水分解は、トリフルオロメチル基が置換しないジハロメチル基置換芳香族化合物と比べて反応速度の遅いことが予測され、鉄塩を触媒とした場合での反応時間の著しい違いは前記の特公昭４８－６９３号と特開２００６－１６０６３５号の各実施例の比較からも容易に見て取れる。
Since the trifluoromethyl group substituted on the aromatic ring is a strong electron-withdrawing group, the hydrolysis of the dihalomethyl group of the aromatic compound substituted with the dihalomethyl group substituted by the trifluoromethyl group is the substitution of the dihalomethyl group not substituted by the trifluoromethyl group. The reaction rate is predicted to be slower than that of the aromatic compound, and the remarkable difference in the reaction time in the case of using an iron salt as a catalyst is the difference between each of the examples of JP-B-48-693 and JP-A-2006-160635. It can be easily seen from the comparison.
また、トリフルオロメチル基を有しないベンザルクロライドに鉄塩の無水物を添加すると直ちに樹脂化することが特公昭４８－６９３号公報に記載されている。
Also, Japanese Patent Publication No. 48-693 describes that when an anhydrous iron salt is added to benzal chloride having no trifluoromethyl group, a resin is formed immediately.
しかしながら、反応開始前に反応原料中にアルデヒド化合物を混入しておくと、そこへ投入した鉄塩は容易に溶解して、通常は鮮やかな赤褐色に着色し、その後昇温してから水を調節しながら添加することにより極めて短時間でトリフルオロメチル基の置換した芳香族アルデヒドが得られることを見出した。
However, if an aldehyde compound is mixed in the reaction raw material before starting the reaction, the iron salt thrown into it is easily dissolved and usually colored bright reddish brown. It was found that an aromatic aldehyde substituted with a trifluoromethyl group can be obtained in a very short time by adding while adding.
すなわち、本発明は次の通りである。
That is, the present invention is as follows.
［発明１］
一般式（１）で表されるジハロメチル基置換芳香族化合物を鉄塩の存在下に加水分解して、一般式（２）で表されるホルミル基置換芳香族化合物を製造する方法であって、加水分解反応が生じる前にアルデヒド化合物と鉄塩を前記ジハロメチル基置換芳香族化合物に溶解することと、加水分解反応が起こるのに十分な反応温度に達した後に水をその消失速度を超えない速度で反応系内へ添加することを含む、前記ホルミル基置換芳香族化合物の製造方法。
（式中、Ａｒは芳香環を表し、Ｘはハロゲン原子を表し、Ｒはそれぞれ独立に異なってよい一価の有機基を表す。ｌは１～３、ｍは１～５、ｎは０～５の整数を表し、１≦ｌ＋ｍ＋ｎ≦６である。）
（式中、Ａｒ、Ｒ、ｌ、ｍ、ｎは一般式（１）と同じ。）
[Invention 1]
A method for producing a formyl group-substituted aromatic compound represented by the general formula (2) by hydrolyzing a dihalomethyl group-substituted aromatic compound represented by the general formula (1) in the presence of an iron salt, Dissolving the aldehyde compound and iron salt in the dihalomethyl group-substituted aromatic compound before the hydrolysis reaction occurs, and the rate at which water is not exceeded after reaching the reaction temperature sufficient for the hydrolysis reaction to occur. The method for producing the above-mentioned formyl group-substituted aromatic compound, which comprises adding the compound into the reaction system in Step 1.
(In the formula, Ar represents an aromatic ring, X represents a halogen atom, R represents a monovalent organic group which may be different from each other, l is 1 to 3, m is 1 to 5, and n is 0 to Represents an integer of 5 and 1 ≦ l + m + n ≦ 6.)
(In the formula, Ar, R, l, m and n are the same as those in the general formula (1).)
一般式（１）で表されるジハロメチル基置換芳香族化合物を鉄塩の存在下に加水分解して、一般式（２）で表されるホルミル基置換芳香族化合物を製造する方法であって、加水分解反応が生じる前にアルデヒド化合物と鉄塩を前記ジハロメチル基置換芳香族化合物に溶解することと、加水分解反応が起こるのに十分な反応温度に達した後に水をその消失速度を超えない速度で反応系内へ添加することを含む、前記ホルミル基置換芳香族化合物の製造方法。
A method for producing a formyl group-substituted aromatic compound represented by the general formula (2) by hydrolyzing a dihalomethyl group-substituted aromatic compound represented by the general formula (1) in the presence of an iron salt, Dissolving the aldehyde compound and iron salt in the dihalomethyl group-substituted aromatic compound before the hydrolysis reaction occurs, and the rate at which water is not exceeded after reaching the reaction temperature sufficient for the hydrolysis reaction to occur. The method for producing the above-mentioned formyl group-substituted aromatic compound, which comprises adding the compound into the reaction system in Step 1.
［発明２］
アルデヒド化合物が、該製造方法で得ようとするホルミル基置換芳香族化合物である、発明１の製造方法。 [Invention 2]
The production method of Invention 1, wherein the aldehyde compound is a formyl group-substituted aromatic compound to be obtained by the production method.
アルデヒド化合物が、該製造方法で得ようとするホルミル基置換芳香族化合物である、発明１の製造方法。 [Invention 2]
The production method of Invention 1, wherein the aldehyde compound is a formyl group-substituted aromatic compound to be obtained by the production method.
［発明３］
アルデヒド化合物が、一般式（３）で表わされるアルデヒド化合物である、発明１のホルミル基置換芳香族化合物の製造方法。
（式中、Ａｒ’は芳香環を表し、Ｒ’はそれぞれ独立にハロゲン原子、ヒドロキシル基、シアノ基、または一価の有機基を表す。ｐは１～５を表す。）
[Invention 3]
The manufacturing method of the formyl group substituted aromatic compound of the invention 1 whose aldehyde compound is an aldehyde compound represented by General formula (3).
(In the formula, Ar ′ represents an aromatic ring, and R ′ each independently represents a halogen atom, a hydroxyl group, a cyano group, or a monovalent organic group. P represents 1 to 5.)
アルデヒド化合物が、一般式（３）で表わされるアルデヒド化合物である、発明１のホルミル基置換芳香族化合物の製造方法。
The manufacturing method of the formyl group substituted aromatic compound of the invention 1 whose aldehyde compound is an aldehyde compound represented by General formula (3).
本発明の方法は、トリフルオロメチル基が置換したジハロメチル基置換芳香族化合物から目的とする芳香族アルデヒドを高い選択率で得ることができ、かつ著しく短時間で反応を完結させることができ、さらに触媒を繰り返し使用できるため、工業的に適した方法である。
The method of the present invention can obtain a desired aromatic aldehyde with high selectivity from a dihalomethyl group-substituted aromatic compound substituted with a trifluoromethyl group, and can complete the reaction in a very short time. Since the catalyst can be used repeatedly, it is an industrially suitable method.
本発明は、トリフルオロメチル基を有する一般式（１）のジハロメチル基置換芳香族化合物を鉄塩の存在下に加水分解して対応する一般式（２）のホルミル基置換芳香族化合物を製造する方法に関する。この製造方法では、加水分解反応が生じる前にアルデヒド化合物と鉄塩が前記ジハロメチル基置換芳香族化合物に溶解され、加水分解反応が起こるのに十分な反応温度に達した後に水をその消失速度を超えない速度で反応系内へ添加する。
In the present invention, a dihalomethyl group-substituted aromatic compound of the general formula (1) having a trifluoromethyl group is hydrolyzed in the presence of an iron salt to produce a corresponding formyl group-substituted aromatic compound of the general formula (2). Regarding the method. In this production method, before the hydrolysis reaction occurs, the aldehyde compound and the iron salt are dissolved in the dihalomethyl group-substituted aromatic compound, and after the reaction temperature is sufficient for the hydrolysis reaction to occur, the water is removed at a rate of disappearance. Add into the reaction system at a rate not exceeding.
一般式（１）において、Ａｒは芳香環を表し、Ｘはハロゲン原子を表し、Ｒはハロゲン原子、ヒドロキシル基、シアノ基、または一価の有機基を表し、ｌは１～３、ｍは１～５、ｎは０～５の整数を表し、１≦ｌ＋ｍ＋ｎ≦６である。また、一般式（２）において、Ａｒ、Ｒ、ｌ、ｍ、ｎは一般式（１）と同じである。
In the general formula (1), Ar represents an aromatic ring, X represents a halogen atom, R represents a halogen atom, a hydroxyl group, a cyano group, or a monovalent organic group, l is 1 to 3, m is 1 ˜5, n represents an integer of 0˜5, and 1 ≦ l + m + n ≦ 6. In the general formula (2), Ar, R, l, m, and n are the same as those in the general formula (1).
Ａｒは、環炭素数４～８の芳香環もしくはそれらの２～１０個が縮合した縮合環であって、その任意の炭素原子が酸素原子、窒素原子、硫黄原子で置換した複素環であってもよい。具体的には、ベンゼン環、ナフタレン環、アントラセン環、ピレン環、フェナントレン環、ペリレン環、コロネン環、ピリジン環、キノリン環、チオフェン環、ピロール環、フラン環などが挙げられるが、ベンゼン環、ナフタレン環、ピリジン環が好ましく、ベンゼン環がより好ましい。
Ar is an aromatic ring having 4 to 8 ring carbon atoms or a condensed ring in which 2 to 10 of them are condensed, and a heterocycle in which any carbon atom is substituted with an oxygen atom, a nitrogen atom, or a sulfur atom, Also good. Specific examples include benzene ring, naphthalene ring, anthracene ring, pyrene ring, phenanthrene ring, perylene ring, coronene ring, pyridine ring, quinoline ring, thiophene ring, pyrrole ring, furan ring, etc., but benzene ring, naphthalene A ring and a pyridine ring are preferable, and a benzene ring is more preferable.
Ｘのハロゲン原子は、フッ素原子、塩素原子、臭素原子または、ヨウ素原子であり、塩素原子または臭素原子が好ましく、塩素がより好ましい。
The halogen atom of X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, preferably a chlorine atom or a bromine atom, and more preferably chlorine.
ジハロメチル基の数ｌは１～３であり、１であるのが好ましい。置換するトリフルオロメチル基の数ｍは１～５であり、１または２が好ましく、１がより好ましく、トリフルオロメチル基以外の置換基Ｒの数ｎは１～５であり、０～２が好ましく、０または１がより好ましい。また、１≦ｌ＋ｍ＋ｎ≦３であるのが好ましい。したがって、ｌ、ｍが共に１であるのが好ましく、ｎは０または１であるのがより好ましい。ジハロメチル基を有する芳香族化合物としては、トリフルオロメチル基とジハロメチル基が隣接する環炭素に置換している芳香族化合物が好ましく、また、塩素原子またはフッ素原子が環炭素にさらに置換している芳香族化合物が好ましく、ここで芳香族としては、ベンゼン環、ナフタレン環またはピリジン環が好ましく、ベンゼン環が特に好ましい。
The number l of dihalomethyl groups is 1 to 3, and is preferably 1. The number m of the substituted trifluoromethyl groups is 1 to 5, preferably 1 or 2, more preferably 1, and the number n of substituents R other than the trifluoromethyl group is 1 to 5, and 0 to 2 is 0 or 1 is more preferable. Moreover, it is preferable that 1 ≦ l + m + n ≦ 3. Accordingly, both l and m are preferably 1, and n is more preferably 0 or 1. The aromatic compound having a dihalomethyl group is preferably an aromatic compound in which a trifluoromethyl group and a dihalomethyl group are substituted on the adjacent ring carbon, and an aromatic compound in which a chlorine atom or a fluorine atom is further substituted on the ring carbon. A group compound is preferable, and as the aromatic, a benzene ring, a naphthalene ring or a pyridine ring is preferable, and a benzene ring is particularly preferable.
本発明では、電子吸引性のトリフルオロメチル基が置換した芳香環に結合したホルミル基の加水分解反応性を向上させることを課題とすることから、トリフルオロメチル基以外のＲで表される一価の有機基としては、特に限定されずに適用されるが、本来電子供与性である置換基ではより容易に反応は進行する。あえて本発明に適用されるＲで表される有機基を例示するならば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子）、ヒドロキシル基、シアノ基、アルキル基、アルケニル基、アルキニル基、アルコキシ基、アリール基、アラルキル基、アリールオキシ基、カルボアルコキシ基、ニトロ基、スルホクロリド基、アルキルスルホニル基、スルホン酸アルキルエステル基、スルホン酸アリールエステル基、置換または非置換のスルホン酸アミド基、メチレンジオキシ基である。これらのＲで表される有機基において、構造中に含まれるアルキル基、アルケニル基、アルキニル基は、それぞれ炭素数１～２０の直鎖状、分岐状または環状のアルキル基、アルケニル基、アルキニル基をいい、アリール基は、芳香族化合物から１個の水素原子が脱離したいわゆる広義のアリール基であって炭素数４～２０のアリール基をいう。また、これらのアルキル基、アルケニル基、アルキニル基、アリール基はさらに置換基を有することができる。この置換基としては、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子）、ヒドロキシル基、シアノ基、アルキル基、アルケニル基、アルキニル基、アルコキシ基、アリール基、アラルキル基、アリールオキシ基、カルボアルコキシ基、ニトロ基、スルホクロリド基、アルキルスルホニル基、スルホン酸アルキルエステル基、スルホン酸アリールエステル基、置換または非置換のスルホン酸アミド基、メチレンジオキシ基が挙げられる。また、構造上含まれる任意の炭素原子は、酸素原子、硫黄原子、窒素原子、カルボニル基で置換することもできる。Ｒとしては、ハロゲン原子、ヒドロキシル基、シアノ基、メチル基、エチル基、ｎ－プロピル基、ｉｓｏ－プロピル基、フェニル基、ペンタフルオロエチル基、２，２，２－トリフルオロエチル基などが好ましく、ハロゲン原子としてはフッ素原子、塩素原子がより好ましい。
In the present invention, since it is an object to improve the hydrolysis reactivity of a formyl group bonded to an aromatic ring substituted with an electron-withdrawing trifluoromethyl group, it is represented by R other than the trifluoromethyl group. The valent organic group is not particularly limited, and the reaction proceeds more easily with a substituent that is inherently electron donating. If the organic group represented by R applied to this invention is illustrated, a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, an iodine atom), a hydroxyl group, a cyano group, an alkyl group, an alkenyl group, an alkynyl group , Alkoxy group, aryl group, aralkyl group, aryloxy group, carboalkoxy group, nitro group, sulfochloride group, alkylsulfonyl group, sulfonic acid alkyl ester group, sulfonic acid aryl ester group, substituted or unsubstituted sulfonic acid amide group , A methylenedioxy group. In these organic groups represented by R, the alkyl group, alkenyl group and alkynyl group contained in the structure are each a linear, branched or cyclic alkyl group, alkenyl group and alkynyl group having 1 to 20 carbon atoms. The aryl group is a so-called broad aryl group in which one hydrogen atom is eliminated from an aromatic compound, and an aryl group having 4 to 20 carbon atoms. Moreover, these alkyl groups, alkenyl groups, alkynyl groups, and aryl groups can further have a substituent. As this substituent, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), hydroxyl group, cyano group, alkyl group, alkenyl group, alkynyl group, alkoxy group, aryl group, aralkyl group, aryloxy group, Examples thereof include a carboalkoxy group, a nitro group, a sulfochloride group, an alkylsulfonyl group, a sulfonic acid alkyl ester group, a sulfonic acid aryl ester group, a substituted or unsubstituted sulfonic acid amide group, and a methylenedioxy group. Any carbon atom contained in the structure can be substituted with an oxygen atom, a sulfur atom, a nitrogen atom or a carbonyl group. R is preferably a halogen atom, hydroxyl group, cyano group, methyl group, ethyl group, n-propyl group, iso-propyl group, phenyl group, pentafluoroethyl group, 2,2,2-trifluoroethyl group or the like. The halogen atom is more preferably a fluorine atom or a chlorine atom.
本発明に使用するジハロメチル基置換芳香族化合物としては、特開昭５９－２１６３７号公報に例示される化合物などを挙げることができ、具体的には、例えば、１－トリフルオロメチル－２－ジハロメチルベンゼン、１－トリフルオロメチル－３－ジハロメチルベンゼン、１－トリフルオロメチル－４－ジハロメチルベンゼン、３－ジハロメチル－４－トリフルオロメチルハロベンゼン、２－トリフルオロメチル－３－ジハロメチルハロベンゼン、３－トリフルオロメチル－４－ジハロメチルハロベンゼン、２－トリフルオロメチル－６－ジハロメチルハロベンゼン、２－ジハロメチル－４－トリフルオロメチルハロベンセン、３－トリフルオロメチル－５－ジハロメチルハロベンゼン、２－トリフルオロメチル－４－ジハロメチルハロベンゼン、２－トリフルオロメチル－５－ジハロメチルハロベンゼン、２－ジハロメチル－５－トリフルオロメチルハロベンセン、１，２－ビス（トリフルオロメチル）－４－ジハロメチルベンゼン、１，４－ビス（トリフルオロメチル）－２－ジハロメチルベンゼン、１，３－ビス（トリフルオロメチル）－５－ジハロメチルベンゼン、１，３－ビス（ジハロメチル）－４－トリフルオロメチルベンゼン、１，３－ビス（ジハロメチル）－５－トリフルオロメチルベンゼン、１，３－ビス（ジハロメチル）－２－トリフルオロメチルベンゼン、１，４－ビス（トリフルオロメチル）－２，５－ビス（ジハロメチル）ベンゼン、１，５－ビス（トリフルオロメチル）－２，４－ビス（ジハロメチル）ベンゼン、１，３，４－トリス（ジハロメチル）－６－トリフルオロメチルベンゼン、２－トリフルオロメチル－４－ジハロメチルビフェニル、３－トリフルオロメチル－４－ジハロメチルビフェニル、２－トリフルオロメチル－３－ジハロメチルビフェニル、３－ハロメチル－４－トリフルオロメチルビフェニル、３－ハロメチル－５－トリフルオロメチルビフェニル、３－ハロメチル－６－トリフルオロメチルビフェニル、１－トリフルオロメチル－３－ジハロメチルナフタレン、１－ジハロメチル－３－トリフルオロメチルナフタレン、１－トリフルオロメチル－２－ジハロメチルナフタレン、１－ジハロメチルー２－トリフルオロメチルナフタレン、１－トリフルオロメナル－４－ジハロメチルナフタレン、１－トリフルオロメチル－５－ジハロメチルナフタレン、２－トリフルオロメチル－３－ジハロメチルナフタレン、２－トリフルオロメチル－６－ジハロメチルナフタレン、２，５－ビス（トリフルオロメチル）－３－ジハロメチルナフタレン、２，８－ビス（トリフルオロメチル）－５－ジハロメチルナフタレン、２，５－ビス（ジハロメチル）－３－トリフルオロメチルナフタレン、２，８－ビス（ジハロメナル）－５－トリフルオロメチルナフタレン、１，３－ビス（ジハロメチル）－５－トリフルオロメチルナフタレン、９－トリフルオメチル－１０－ジハロメチルアントラセン、９－ジハロメチル－１０－トリフルオロメチルアントラセン、２－ジハロメチル－３－ハロ－５－トリフルオロメチルピリジン、２－ジハロメチル－３－トリフルオロメチルピリジン、２－ジハロメチル－４－トリフルオロメチルピリジン、２－トリフルオロメチル－４－ジハロメチルピリジン、２－トリフルオロメチル－５－ジハロメチルピリジン、２－ジハロメチル－５－トリフルオロメチルピリジン、２－トリフルオロメチル－６－ジハロメチルピリジン、３－ジハロメチル－４－トリフルオロメチルピリジン、３－トリフルオロメチル－４－ジハロメチルピリジン、３－トリフルオロメチル－５－ジハロメチルビリジン、２－トリフルオロメチル－４－ジハロメチルキノリン、２－ジハロメチル－４－トリフルオロメチルキノリン、２－トリフルオロメチル－６－ジハロメチルキノリン、２－ジハロメチル－６－トリフルオロメチルキノリン等が挙げられるがこれらに限られない。ここでジハロメチル基の「ハロ」は「クロロ」または「ブロモ」と読み、ハロ基（芳香環へ置換するハロゲン原子）の「ハロ」は「クロロ」または「フルオロ」と読む。ジハロメチル基はジクロロメチル基であるのが好ましい。
Examples of the dihalomethyl group-substituted aromatic compound used in the present invention include compounds exemplified in JP 59-21637 A, and specifically, for example, 1-trifluoromethyl-2-di Halomethylbenzene, 1-trifluoromethyl-3-dihalomethylbenzene, 1-trifluoromethyl-4-dihalomethylbenzene, 3-dihalomethyl-4-trifluoromethylhalobenzene, 2-trifluoromethyl-3- Dihalomethylhalobenzene, 3-trifluoromethyl-4-dihalomethylhalobenzene, 2-trifluoromethyl-6-dihalomethylhalobenzene, 2-dihalomethyl-4-trifluoromethylhalobenzene, 3-trifluoro Methyl-5-dihalomethylhalobenzene, 2-trifluoromethyl-4-dihalomethylhalo , 2-trifluoromethyl-5-dihalomethylhalobenzene, 2-dihalomethyl-5-trifluoromethylhalobencene, 1,2-bis (trifluoromethyl) -4-dihalomethylbenzene, 1,4- Bis (trifluoromethyl) -2-dihalomethylbenzene, 1,3-bis (trifluoromethyl) -5-dihalomethylbenzene, 1,3-bis (dihalomethyl) -4-trifluoromethylbenzene, 1, 3-bis (dihalomethyl) -5-trifluoromethylbenzene, 1,3-bis (dihalomethyl) -2-trifluoromethylbenzene, 1,4-bis (trifluoromethyl) -2,5-bis (dihalomethyl) benzene 1,5-bis (trifluoromethyl) -2,4-bis (dihalomethyl) benzene, 1,3,4-tris (dihalomethyl) ) -6-trifluoromethylbenzene, 2-trifluoromethyl-4-dihalomethylbiphenyl, 3-trifluoromethyl-4-dihalomethylbiphenyl, 2-trifluoromethyl-3-dihalomethylbiphenyl, 3 -Halomethyl-4-trifluoromethylbiphenyl, 3-halomethyl-5-trifluoromethylbiphenyl, 3-halomethyl-6-trifluoromethylbiphenyl, 1-trifluoromethyl-3-dihalomethylnaphthalene, 1-dihalomethyl-3 -Trifluoromethylnaphthalene, 1-trifluoromethyl-2-dihalomethylnaphthalene, 1-dihalomethyl-2-trifluoromethylnaphthalene, 1-trifluoromenal-4-dihalomethylnaphthalene, 1-trifluoromethyl-5 Dihalomethylnaphthalene, 2-trif Fluoromethyl-3-dihalomethylnaphthalene, 2-trifluoromethyl-6-dihalomethylnaphthalene, 2,5-bis (trifluoromethyl) -3-dihalomethylnaphthalene, 2,8-bis (trifluoromethyl) -5-dihalomethylnaphthalene, 2,5-bis (dihalomethyl) -3-trifluoromethylnaphthalene, 2,8-bis (dihalomenal) -5-trifluoromethylnaphthalene, 1,3-bis (dihalomethyl) -5 -Trifluoromethylnaphthalene, 9-trifluoromethyl-10-dihalomethylanthracene, 9-dihalomethyl-10-trifluoromethylanthracene, 2-dihalomethyl-3-halo-5-trifluoromethylpyridine, 2-dihalomethyl-3- Trifluoromethylpyridine, 2-dihalomethyl-4-trifluoro Methylpyridine, 2-trifluoromethyl-4-dihalomethylpyridine, 2-trifluoromethyl-5-dihalomethylpyridine, 2-dihalomethyl-5-trifluoromethylpyridine, 2-trifluoromethyl-6-dihalo Methylpyridine, 3-dihalomethyl-4-trifluoromethylpyridine, 3-trifluoromethyl-4-dihalomethylpyridine, 3-trifluoromethyl-5-dihalomethylviridine, 2-trifluoromethyl-4-dihalo Examples thereof include, but are not limited to, methyl quinoline, 2-dihalomethyl-4-trifluoromethyl quinoline, 2-trifluoromethyl-6-dihalomethyl quinoline, 2-dihalomethyl-6-trifluoromethyl quinoline. Here, “halo” of the dihalomethyl group is read as “chloro” or “bromo”, and “halo” of the halo group (halogen atom substituted on the aromatic ring) is read as “chloro” or “fluoro”. The dihalomethyl group is preferably a dichloromethyl group.
これらのジハロメチル基を有する芳香族化合物は、公知の方法で対応する化合物のメチル基をハロゲン化剤でハロゲン化することで得られる。例えば、三塩化リンなどの塩素化剤により塩素化することで、トリクロロメチル基を有する化合物、ジクロロメチル基を有する化合物とともに得ることができる。
These aromatic compounds having a dihalomethyl group can be obtained by halogenating the methyl group of the corresponding compound with a halogenating agent by a known method. For example, it can be obtained together with a compound having a trichloromethyl group and a compound having a dichloromethyl group by chlorinating with a chlorinating agent such as phosphorus trichloride.
本発明の方法で得られる一般式（２）で表されるホルミル基置換芳香族化合物は、原料として使用した一般式（１）で表されるジハロメチル基置換芳香族化合物のジハロメチル基がホルミル基に変換された化合物であり他の部分構造に変化は起こらない。
In the formyl group-substituted aromatic compound represented by the general formula (2) obtained by the method of the present invention, the dihalomethyl group of the dihalomethyl group-substituted aromatic compound represented by the general formula (1) used as a raw material is a formyl group. It is a converted compound and other partial structures do not change.
本発明に使用する鉄塩は、鉄のハロゲン化物であり、塩化第二鉄、塩化第一鉄、臭化第二鉄、臭化第一鉄が挙げられ、塩化第二鉄が最も好ましい。これらの鉄塩の水和物を使用することもできる。また、鉄塩は予め錯体に調製して使用できる。鉄塩の使用量は、原料の一般式（１）で表されるジハロメチル基置換芳香族化合物の０．１～３０質量％であり、０．５～２０質量％が好ましく、１～１０質量％がより好ましい。０．１質量％未満では十分な活性が得られず、３０質量％を超えるのは反応の面では問題ないが後処理が煩雑になるのでそれぞれ好ましくない。
The iron salt used in the present invention is an iron halide, and examples thereof include ferric chloride, ferrous chloride, ferric bromide, and ferrous bromide, and ferric chloride is most preferable. Hydrates of these iron salts can also be used. Further, the iron salt can be prepared in advance as a complex and used. The amount of the iron salt used is 0.1 to 30% by mass, preferably 0.5 to 20% by mass of the dihalomethyl group-substituted aromatic compound represented by the general formula (1) of the raw material, and 1 to 10% by mass. Is more preferable. If it is less than 0.1% by mass, sufficient activity cannot be obtained, and if it exceeds 30% by mass, there is no problem in terms of reaction, but the post-treatment becomes complicated, which is not preferable.
本発明において、加水分解反応が生じる前に原料となる一般式（１）で表されるジハロメチル基置換芳香族化合物に添加しておくアルデヒド化合物としては、ホルミル基が環に結合したアルデヒド化合物であれば特に限定されないが、目的とする一般式（２）で表されるホルミル基置換芳香族化合物と沸点差の大きいものが好ましい。このようなアルデヒド化合物としては、一般式（３）で表されるアルデヒド化合物が挙げられる。
（式中、Ａｒ’は芳香環を表し、Ｒ’はそれぞれ独立にハロゲン原子、ヒドロキシル基、シアノ基、または一価の有機基を表す。ｐは１～５を表す。）
Ａｒ’で表される芳香環は前記Ａｒと同様の芳香環であればよい。Ｒ’における一価の有機基は、前記Ｒと同様の一価の有機基またはトリフルオロメチル基である。このアルデヒド化合物は、本発明にかかるジハロメチル基置換芳香族化合物に溶解することが必要であるので、ベンゼン環を有することと、鉄塩を溶解するためにホルミル基を有することが必要である。 In the present invention, the aldehyde compound added to the dihalomethyl group-substituted aromatic compound represented by the general formula (1) used as a raw material before hydrolysis reaction occurs may be an aldehyde compound in which a formyl group is bonded to a ring. Although not particularly limited, those having a large difference in boiling point from the target formyl group-substituted aromatic compound represented by the general formula (2) are preferable. Examples of such aldehyde compounds include aldehyde compounds represented by the general formula (3).
(In the formula, Ar ′ represents an aromatic ring, and R ′ each independently represents a halogen atom, a hydroxyl group, a cyano group, or a monovalent organic group. P represents 1 to 5.)
The aromatic ring represented by Ar ′ may be the same aromatic ring as Ar. The monovalent organic group in R ′ is the same monovalent organic group or trifluoromethyl group as R. Since this aldehyde compound needs to be dissolved in the dihalomethyl group-substituted aromatic compound according to the present invention, it must have a benzene ring and a formyl group in order to dissolve the iron salt.
Ａｒ’で表される芳香環は前記Ａｒと同様の芳香環であればよい。Ｒ’における一価の有機基は、前記Ｒと同様の一価の有機基またはトリフルオロメチル基である。このアルデヒド化合物は、本発明にかかるジハロメチル基置換芳香族化合物に溶解することが必要であるので、ベンゼン環を有することと、鉄塩を溶解するためにホルミル基を有することが必要である。 In the present invention, the aldehyde compound added to the dihalomethyl group-substituted aromatic compound represented by the general formula (1) used as a raw material before hydrolysis reaction occurs may be an aldehyde compound in which a formyl group is bonded to a ring. Although not particularly limited, those having a large difference in boiling point from the target formyl group-substituted aromatic compound represented by the general formula (2) are preferable. Examples of such aldehyde compounds include aldehyde compounds represented by the general formula (3).
The aromatic ring represented by Ar ′ may be the same aromatic ring as Ar. The monovalent organic group in R ′ is the same monovalent organic group or trifluoromethyl group as R. Since this aldehyde compound needs to be dissolved in the dihalomethyl group-substituted aromatic compound according to the present invention, it must have a benzene ring and a formyl group in order to dissolve the iron salt.
具体的には、ベンゾアルデヒド、２－クロロベンゾアルデヒド、３－クロロベンゾアルデヒド、４－クロロベンゾアルデヒド、２－ブロモベンゾアルデヒド、３－ブロモベンゾアルデヒド、４－ブロモベンゾアルデヒド、２－メチルベンゾアルデヒド、３－メチルベンゾアルデヒド、４－メチルベンゾアルデヒド、２－エチルベンゾアルデヒド、３－エチルベンゾアルデヒド、４－エチルベンゾアルデヒド、２－ｔ－ブチルベンゾアルデヒド、３－ｔ－ブチルメチルベンゾアルデヒド、４－ｔ－ブチルメチルベンゾアルデヒド、２－メトキシベンゾアルデヒド、３－メトキシベンゾアルデヒド、４－メトキシベンゾアルデヒド、２－シアノベンゾアルデヒド、３－シアノベンゾアルデヒド、４－シアノベンゾアルデヒドなど、また、前記一般式（１）で表されるジハロメチル基置換芳香族化合物として例示した化合物のそれぞれに対応する生成物である一般式（２）で表されるホルミル基置換芳香族化合物を挙げることができる。これらのアルデヒド化合物は当該反応の目的生成物であるのが、蒸留などによる精製操作が容易であり最も好ましい。
Specifically, benzaldehyde, 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-methylbenzaldehyde, 3-methylbenzaldehyde, 4-methylbenzaldehyde, 2-ethylbenzaldehyde, 3-ethylbenzaldehyde, 4-ethylbenzaldehyde, 2-t-butylbenzaldehyde, 3-t-butylmethylbenzaldehyde, 4-t -Butylmethylbenzaldehyde, 2-methoxybenzaldehyde, 3-methoxybenzaldehyde, 4-methoxybenzaldehyde, 2-cyanobenzaldehyde, 3-cyanobenzaldehyde, 4-cyanobenzaldehyde, etc. Can be exemplified formyl group-substituted aromatic compound represented by the general formula is a product corresponding to each of the compounds exemplified as dihalomethyl-substituted aromatic compound represented by the formula (1) (2). These aldehyde compounds are the desired products of the reaction, and are most preferred because they can be easily purified by distillation or the like.
アルデヒド化合物の添加量は、原料の一般式（１）で表されるトリフルオロメチル基含有芳香族化合物１質量部に対し、０．００１～１００質量部であり、０．００５～１質量部が好ましく、０．０１～０．１質量部がより好ましい。
The amount of the aldehyde compound added is 0.001 to 100 parts by mass, and 0.005 to 1 part by mass with respect to 1 part by mass of the trifluoromethyl group-containing aromatic compound represented by the general formula (1) of the raw material. Preferably, 0.01 to 0.1 part by mass is more preferable.
一般式（１）で表されるジハロメチル基置換芳香族化合物またはそれから得られる生成物が固体または粘稠な液体などの場合は、反応系中に適切な溶媒を添加してもよい。使用する溶媒は、本発明の反応条件において不活性な液体であり、例えば、テトラクロロエチレン、１，２－ジクロロエタンなどのハロゲン化炭化水素類、トルエン、キシレン、メシチレンなどの芳香族炭化水素、クロロベンゼンなどのハロゲン化芳香族化合物などが例示できる。
When the dihalomethyl group-substituted aromatic compound represented by the general formula (1) or the product obtained therefrom is a solid or a viscous liquid, an appropriate solvent may be added to the reaction system. The solvent used is a liquid that is inert under the reaction conditions of the present invention, and examples thereof include halogenated hydrocarbons such as tetrachloroethylene and 1,2-dichloroethane, aromatic hydrocarbons such as toluene, xylene, and mesitylene, and chlorobenzene. A halogenated aromatic compound etc. can be illustrated.
本発明の方法においては、水は反応系に徐々に添加することが必要である。すなわち、水の添加速度は反応系に液体の水が滞留することのないように、加水分解反応で消費されるよりも遅い速度を保つ。したがって、反応基質の種類、触媒としての鉄塩の量、反応温度によって水の添加速度は決定される。水の添加量の総量は、加水分解反応で副生するハロゲン化水素に水蒸気が同伴して系外に持ち出されることがあるために、反応の原料である一般式（１）で表されるジハロメチル基置換芳香族化合物１モルに対し１モルよりも若干多めに使用するが、１～２モルでよく、通常１．１モル程度の量とする。１モル未満では加水分解が完結せず、過剰に用いた水は水の層を形成して反応に寄与せず、しかも加水分解速度が著しく低下するため好ましくない。
In the method of the present invention, it is necessary to gradually add water to the reaction system. That is, the rate of water addition is kept slower than that consumed in the hydrolysis reaction so that liquid water does not stay in the reaction system. Therefore, the rate of water addition is determined by the type of reaction substrate, the amount of iron salt as a catalyst, and the reaction temperature. The total amount of water added is dihalomethyl represented by the general formula (1), which is a raw material for the reaction, because the hydrogen halide produced as a by-product in the hydrolysis reaction is sometimes accompanied by water vapor. Although it is used slightly more than 1 mol per 1 mol of the group-substituted aromatic compound, it may be 1 to 2 mol, and is usually about 1.1 mol. If the amount is less than 1 mole, hydrolysis is not completed, and excessively used water is not preferable because it forms a water layer and does not contribute to the reaction, and the hydrolysis rate is significantly reduced.
本発明の方法では、反応温度は４０℃以上で反応液の沸点以下で行うが、通常４０～２００℃で行うことができ、８０～１６０℃が好ましく、９０～１４０℃がより好ましい。４０℃以下では反応が遅く実用的でない。また、反応温度が２００℃を超えると重合反応が起きることがあり好ましくない。
In the method of the present invention, the reaction temperature is 40 ° C. or higher and below the boiling point of the reaction solution, but it can be usually 40 to 200 ° C., preferably 80 to 160 ° C., more preferably 90 to 140 ° C. Below 40 ° C, the reaction is slow and impractical. Moreover, when the reaction temperature exceeds 200 ° C., a polymerization reaction may occur, which is not preferable.
反応圧力は特に限定されないが、０．０５～１ＭＰａで行えばよい。
The reaction pressure is not particularly limited, but may be 0.05 to 1 MPa.
反応に使用する容器は、ガラス容器、ガラスライニング容器、フッ素樹脂容器などが使用できるがこれらの材質に限られない。反応は、バッチ式、半流通式、流通式などいずれの形式でも実施可能である。
The container used for the reaction can be a glass container, a glass lining container, a fluororesin container or the like, but is not limited to these materials. The reaction can be carried out in any form such as batch, semi-flow, and flow.
本発明の方法をバッチ式で行う場合を例示的に説明する。連続式で行う場合にはこの記載に基づいて当業者が当技術分野の常識に基づいて容易に変更を加えることができる。
The case where the method of the present invention is performed in a batch manner will be described as an example. In the case of continuous operation, those skilled in the art can easily make changes based on this description based on common sense in the art.
反応容器に原料としてジハロメチル基置換芳香族化合物と所定量のアルデヒド化合物を仕込み、そこへ鉄塩を添加する。一般式（１）で表されるジハロメチル基置換芳香族化合物は通常塩化第二鉄などの無機鉄塩をほとんど溶解しないので、アルデヒド化合物に予め溶解しておくことも好ましい。鉄塩は溶解して反応器の内容物は赤褐色等に着色することが多い。この溶液を加熱して反応温度に達した時に、反応系内に水滴が滞留しないように加水分解速度に合わせて徐々に水を添加すると、塩化水素の発生が見られ加水分解反応の進行が分かる。所定量の水を添加するか、所定量の塩化水素の発生を確認するか、または反応液の色調の変化によっても反応の終了を知ることができる。また、高速液体クロマトグラフィ（ＨＰＬＣ）またはガスクロマトグラフィ（ＧＣ）で原料の消失または生成物の最大化により確認することもできる。水の添加を停止した後、反応容器内の生成物を加熱および／または減圧して蒸留等することで一般式（２）で表わされるホルミル基置換芳香族化合物を取得することができる。生成物を留去して反応器内に残存した鉄塩は実施例において示すように触媒活性を失わないので繰り返し同一の反応に使用することができる。このとき、生成物も次の反応に必要な所定量を残留させておくのが好ましい。
The reaction vessel is charged with a dihalomethyl group-substituted aromatic compound and a predetermined amount of aldehyde compound as raw materials, and an iron salt is added thereto. Since the dihalomethyl group-substituted aromatic compound represented by the general formula (1) usually does not substantially dissolve inorganic iron salts such as ferric chloride, it is also preferable to dissolve in advance in the aldehyde compound. In many cases, the iron salt dissolves and the contents of the reactor are colored reddish brown. When this solution is heated to reach the reaction temperature, water is gradually added at the hydrolysis rate so that water droplets do not stay in the reaction system, and hydrogen chloride is generated, indicating the progress of the hydrolysis reaction. . The completion of the reaction can be known also by adding a predetermined amount of water, confirming the generation of a predetermined amount of hydrogen chloride, or changing the color tone of the reaction solution. It can also be confirmed by high-performance liquid chromatography (HPLC) or gas chromatography (GC) by disappearance of raw materials or maximization of products. After stopping the addition of water, the formyl group-substituted aromatic compound represented by the general formula (2) can be obtained by heating and / or reducing the pressure in the reaction vessel and distilling the product. The iron salt remaining in the reactor after distilling off the product does not lose its catalytic activity as shown in the examples, so that it can be used repeatedly in the same reaction. At this time, it is preferable to leave a predetermined amount of the product necessary for the next reaction.
以下に実施例をもって本発明を説明するが、本発明はこれらの実施例に限られない。
Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to these examples.
［実施例１］
ジムロート冷却管を取り付けた２５ｍｌ三角フラスコに、純度９９．８％のオルソ－トリフルオロメチルベンザルクロライド（１－トリフルオロメチル－２－ジクロロメチルベンゼン、「ＯＴＦＢＡＣ」と略す。）：５ｇ、純度９９．５％のオルソ－トリフルオロメチルベンズアルデヒド（２－トリフルオロメチルベンズアルデヒド、「ＯＴＦＢＡＤ」と略す。）：１ｇ、無水・塩化第二鉄（粉状）：０．０４５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１２０℃に達した時点で、２５μＬシリンジで純水約０．４７ｇを約１０分間かけて順次滴下した。滴下後、１２２～１３１℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．８％がＯＴＦＢＡＤであった。 [Example 1]
In a 25 ml Erlenmeyer flask equipped with a Dimroth condenser, ortho-trifluoromethylbenzal chloride (1-trifluoromethyl-2-dichloromethylbenzene, abbreviated as “OTFBAC”) having a purity of 99.8%: 5 g, purity 99 5% ortho-trifluoromethylbenzaldehyde (2-trifluoromethylbenzaldehyde, abbreviated as “OTFBAD”): 1 g, anhydrous / ferric chloride (powder): 0.045 g, put in a magnetic stirrer Heated with stirring. When the liquid temperature reached about 120 ° C., about 0.47 g of pure water was sequentially added dropwise over about 10 minutes with a 25 μL syringe. After the dropwise addition, the reaction was completed by stirring at 122-131 ° C. for about 10 minutes. As a result of analyzing the reaction liquid by gas chromatography, 99.8% was OTFFBAD.
ジムロート冷却管を取り付けた２５ｍｌ三角フラスコに、純度９９．８％のオルソ－トリフルオロメチルベンザルクロライド（１－トリフルオロメチル－２－ジクロロメチルベンゼン、「ＯＴＦＢＡＣ」と略す。）：５ｇ、純度９９．５％のオルソ－トリフルオロメチルベンズアルデヒド（２－トリフルオロメチルベンズアルデヒド、「ＯＴＦＢＡＤ」と略す。）：１ｇ、無水・塩化第二鉄（粉状）：０．０４５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１２０℃に達した時点で、２５μＬシリンジで純水約０．４７ｇを約１０分間かけて順次滴下した。滴下後、１２２～１３１℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．８％がＯＴＦＢＡＤであった。 [Example 1]
In a 25 ml Erlenmeyer flask equipped with a Dimroth condenser, ortho-trifluoromethylbenzal chloride (1-trifluoromethyl-2-dichloromethylbenzene, abbreviated as “OTFBAC”) having a purity of 99.8%: 5 g, purity 99 5% ortho-trifluoromethylbenzaldehyde (2-trifluoromethylbenzaldehyde, abbreviated as “OTFBAD”): 1 g, anhydrous / ferric chloride (powder): 0.045 g, put in a magnetic stirrer Heated with stirring. When the liquid temperature reached about 120 ° C., about 0.47 g of pure water was sequentially added dropwise over about 10 minutes with a 25 μL syringe. After the dropwise addition, the reaction was completed by stirring at 122-131 ° C. for about 10 minutes. As a result of analyzing the reaction liquid by gas chromatography, 99.8% was OTFFBAD.
［実施例２］
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９９．２％のＯＴＦＢＡＣ：５０ｇ、純度９９．０％のＯＴＦＢＡＤ：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３０℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．２ｇを、約１０分間かけて順次滴下した。滴下後、１２６～１３４℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．０％がＯＴＦＢＡＤであった。得られた生成物を単蒸留にかけて７２～７５℃／２０ｍｍＨｇの留分として純度９９．８％のＯＴＦＢＡＤ（収率：９４．８％）３６．１ｇを得た。塩化鉄を含むＯＴＦＢＡＤ残渣は、５．６ｇであった。 [Example 2]
Into a 100 ml Erlenmeyer flask equipped with a Dimroth condenser, put 50 g of OTFBAC with a purity of 99.2%, 5 g of OTFBAD with a purity of 99.0%, and 0.25 g of anhydrous ferric chloride (powder): Heat with stirring with a tic stirrer. When the liquid temperature reached about 130 ° C., 4.2 g of pure water was successively added dropwise over about 10 minutes with a Pasteur pipette (1 ml). After the dropwise addition, the reaction was completed by stirring at 126 to 134 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.0% was OTFFBAD. The obtained product was subjected to simple distillation to obtain 36.1 g of OTFBAD (yield: 94.8%) having a purity of 99.8% as a fraction of 72 to 75 ° C./20 mmHg. The OTFBAD residue containing iron chloride was 5.6 g.
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９９．２％のＯＴＦＢＡＣ：５０ｇ、純度９９．０％のＯＴＦＢＡＤ：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３０℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．２ｇを、約１０分間かけて順次滴下した。滴下後、１２６～１３４℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．０％がＯＴＦＢＡＤであった。得られた生成物を単蒸留にかけて７２～７５℃／２０ｍｍＨｇの留分として純度９９．８％のＯＴＦＢＡＤ（収率：９４．８％）３６．１ｇを得た。塩化鉄を含むＯＴＦＢＡＤ残渣は、５．６ｇであった。 [Example 2]
Into a 100 ml Erlenmeyer flask equipped with a Dimroth condenser, put 50 g of OTFBAC with a purity of 99.2%, 5 g of OTFBAD with a purity of 99.0%, and 0.25 g of anhydrous ferric chloride (powder): Heat with stirring with a tic stirrer. When the liquid temperature reached about 130 ° C., 4.2 g of pure water was successively added dropwise over about 10 minutes with a Pasteur pipette (1 ml). After the dropwise addition, the reaction was completed by stirring at 126 to 134 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.0% was OTFFBAD. The obtained product was subjected to simple distillation to obtain 36.1 g of OTFBAD (yield: 94.8%) having a purity of 99.8% as a fraction of 72 to 75 ° C./20 mmHg. The OTFBAD residue containing iron chloride was 5.6 g.
［実施例３～１１］
実施例２で得られた塩化鉄を含むＯＴＦＢＡＤ残渣に新たにＯＴＦＢＡＣを５０ｇ仕込んで、実施例２と同じ試験を行った。反応温度、純水の添加時間、添加水量とＯＴＦＢＡＤの収量を表１に示した（実施例３）。さらに、同じ試験を繰り返し（実施例４～１１）そのときの諸元を表１に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
[Examples 3 to 11]
50 g of OTFBAC was newly added to the OTFBAD residue containing iron chloride obtained in Example 2, and the same test as in Example 2 was performed. The reaction temperature, the addition time of pure water, the amount of added water and the yield of OTFBAD are shown in Table 1 (Example 3). Further, the same test was repeated (Examples 4 to 11). Table 1 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
実施例２で得られた塩化鉄を含むＯＴＦＢＡＤ残渣に新たにＯＴＦＢＡＣを５０ｇ仕込んで、実施例２と同じ試験を行った。反応温度、純水の添加時間、添加水量とＯＴＦＢＡＤの収量を表１に示した（実施例３）。さらに、同じ試験を繰り返し（実施例４～１１）そのときの諸元を表１に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
50 g of OTFBAC was newly added to the OTFBAD residue containing iron chloride obtained in Example 2, and the same test as in Example 2 was performed. The reaction temperature, the addition time of pure water, the amount of added water and the yield of OTFBAD are shown in Table 1 (Example 3). Further, the same test was repeated (Examples 4 to 11). Table 1 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
［実施例１２］
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９８．４％の２－トリフルオロメチル－５－フルオロベンザルクロライド（「２ＴＦ５ＦＢＡＣ」と略す。）：５０ｇ、純度９９．８％の２－トリフルオロメチル－５－フルオロベンズアルデヒド（「２ＴＦ５ＦＢＡＤ」と略す。）：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３０℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．５ｇを、約１０分間かけて順次滴下した。滴下後、１２８～１３６℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．１％が２ＴＦ５ＦＢＡＤであった。得られた生成物を単蒸留にかけて６５～６８℃／２０ｍｍＨｇの留分として純度９９．８％の２ＴＦ５ＦＢＡＤ（収率：８５．６％）３７．０ｇを得た。塩化鉄を含む２ＴＦ５ＦＢＡＤ残渣は、６．９ｇであった。 [Example 12]
A 100 ml Erlenmeyer flask equipped with a Dimroth condenser was charged with 98.4% 2-trifluoromethyl-5-fluorobenzal chloride (abbreviated as “2TF5FBAC”): 50 g, 99.8% purity 2-trifluoro. Methyl-5-fluorobenzaldehyde (abbreviated as “2TF5FBAD”): 5 g and anhydrous / ferric chloride (powder): 0.25 g were added and heated with stirring with a magnetic stirrer. When the liquid temperature reached about 130 ° C., 4.5 g of pure water was successively added dropwise over about 10 minutes with a Pasteur pipette (1 ml). After the dropwise addition, the reaction was terminated by stirring at 128 to 136 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.1% was 2TF5FBAD. The obtained product was subjected to simple distillation to obtain 37.0 g of 2TF5FBAD having a purity of 99.8% (yield: 85.6%) as a fraction of 65 to 68 ° C./20 mmHg. The 2TF5FBAD residue containing iron chloride was 6.9 g.
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９８．４％の２－トリフルオロメチル－５－フルオロベンザルクロライド（「２ＴＦ５ＦＢＡＣ」と略す。）：５０ｇ、純度９９．８％の２－トリフルオロメチル－５－フルオロベンズアルデヒド（「２ＴＦ５ＦＢＡＤ」と略す。）：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３０℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．５ｇを、約１０分間かけて順次滴下した。滴下後、１２８～１３６℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．１％が２ＴＦ５ＦＢＡＤであった。得られた生成物を単蒸留にかけて６５～６８℃／２０ｍｍＨｇの留分として純度９９．８％の２ＴＦ５ＦＢＡＤ（収率：８５．６％）３７．０ｇを得た。塩化鉄を含む２ＴＦ５ＦＢＡＤ残渣は、６．９ｇであった。 [Example 12]
A 100 ml Erlenmeyer flask equipped with a Dimroth condenser was charged with 98.4% 2-trifluoromethyl-5-fluorobenzal chloride (abbreviated as “2TF5FBAC”): 50 g, 99.8% purity 2-trifluoro. Methyl-5-fluorobenzaldehyde (abbreviated as “2TF5FBAD”): 5 g and anhydrous / ferric chloride (powder): 0.25 g were added and heated with stirring with a magnetic stirrer. When the liquid temperature reached about 130 ° C., 4.5 g of pure water was successively added dropwise over about 10 minutes with a Pasteur pipette (1 ml). After the dropwise addition, the reaction was terminated by stirring at 128 to 136 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.1% was 2TF5FBAD. The obtained product was subjected to simple distillation to obtain 37.0 g of 2TF5FBAD having a purity of 99.8% (yield: 85.6%) as a fraction of 65 to 68 ° C./20 mmHg. The 2TF5FBAD residue containing iron chloride was 6.9 g.
［実施例１３～２１］
実施例１２で得られた塩化鉄を含む２ＴＦ５ＦＢＡＤ残渣に、新たに２ＴＦ５ＦＢＡＣを５０ｇ仕込んで、実施例１２と同じ試験を行った。反応温度、純水の添加時間、添加水量と２ＴＦ５ＦＢＡＤの収量を表２に示した。さらに、同じ試験を繰り返し（実施例１４～２１）そのときの諸元を表２に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
[Examples 13 to 21]
50 g of 2TF5FBAC was newly added to the 2TF5FBAD residue containing iron chloride obtained in Example 12, and the same test as in Example 12 was performed. Table 2 shows the reaction temperature, the addition time of pure water, the amount of added water, and the yield of 2TF5FBAD. Further, the same test was repeated (Examples 14 to 21). Table 2 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
実施例１２で得られた塩化鉄を含む２ＴＦ５ＦＢＡＤ残渣に、新たに２ＴＦ５ＦＢＡＣを５０ｇ仕込んで、実施例１２と同じ試験を行った。反応温度、純水の添加時間、添加水量と２ＴＦ５ＦＢＡＤの収量を表２に示した。さらに、同じ試験を繰り返し（実施例１４～２１）そのときの諸元を表２に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
50 g of 2TF5FBAC was newly added to the 2TF5FBAD residue containing iron chloride obtained in Example 12, and the same test as in Example 12 was performed. Table 2 shows the reaction temperature, the addition time of pure water, the amount of added water, and the yield of 2TF5FBAD. Further, the same test was repeated (Examples 14 to 21). Table 2 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
［実施例２２］
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９９．１％の４－クロロ－２－トリフルオロメチルベンザルクロライド（４Ｃ２ＴＦＢＡＣと略す）：５０ｇ、純度９９．９％の４－クロロ－２－トリフルオロメチルベンズアルデヒド（４Ｃ２ＴＦＢＡＤと略す）：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３５℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．８ｇを、約１０分間かけて順次滴下した。滴下後、１３０～１３７℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．３％が４Ｃ２ＴＦＢＡＤであった。得られた生成物を単蒸留にかけて６５～７２℃／２０ｍｍＨｇの留分として純度９９．８％の４Ｃ２ＴＦＢＡＤ（収率：９９．５％）３８．８ｇを得た。塩化鉄を含む４Ｃ２ＴＦＢＡＤ残渣は、４．９ｇであった。 [Example 22]
A 100 ml Erlenmeyer flask equipped with a Dimroth condenser was charged with 99.1% purity 4-chloro-2-trifluoromethylbenzal chloride (abbreviated as 4C2TFBAC): 50 g, 99.9% purity 4-chloro-2-tri Fluoromethylbenzaldehyde (abbreviated as 4C2TFBAD): 5 g and anhydrous / ferric chloride (powder): 0.25 g were added and heated while stirring with a magnetic stirrer. When the liquid temperature reached about 135 ° C., 4.8 g of pure water was successively dropped over about 10 minutes with a Pasteur pipette (1 ml). After the dropping, the reaction was completed by stirring at 130 to 137 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.3% was 4C2TFBAD. The obtained product was subjected to simple distillation to obtain 38.8 g of 4C2TFBAD having a purity of 99.8% (yield: 99.5%) as a fraction of 65 to 72 ° C./20 mmHg. The 4C2TFBAD residue containing iron chloride was 4.9 g.
ジムロート冷却管を取り付けた１００ｍｌ三角フラスコに、純度９９．１％の４－クロロ－２－トリフルオロメチルベンザルクロライド（４Ｃ２ＴＦＢＡＣと略す）：５０ｇ、純度９９．９％の４－クロロ－２－トリフルオロメチルベンズアルデヒド（４Ｃ２ＴＦＢＡＤと略す）：５ｇ、無水・塩化第二鉄（粉状）：０．２５ｇを入れて、マグネチックスターラーで攪拌しながら加熱した。液温が約１３５℃に達した時点で、パスツールピペット（１ｍｌ）で純水４．８ｇを、約１０分間かけて順次滴下した。滴下後、１３０～１３７℃で約１０分間攪拌して反応を終えた。反応液をガスクロマトグラフィで分析した結果、９９．３％が４Ｃ２ＴＦＢＡＤであった。得られた生成物を単蒸留にかけて６５～７２℃／２０ｍｍＨｇの留分として純度９９．８％の４Ｃ２ＴＦＢＡＤ（収率：９９．５％）３８．８ｇを得た。塩化鉄を含む４Ｃ２ＴＦＢＡＤ残渣は、４．９ｇであった。 [Example 22]
A 100 ml Erlenmeyer flask equipped with a Dimroth condenser was charged with 99.1% purity 4-chloro-2-trifluoromethylbenzal chloride (abbreviated as 4C2TFBAC): 50 g, 99.9% purity 4-chloro-2-tri Fluoromethylbenzaldehyde (abbreviated as 4C2TFBAD): 5 g and anhydrous / ferric chloride (powder): 0.25 g were added and heated while stirring with a magnetic stirrer. When the liquid temperature reached about 135 ° C., 4.8 g of pure water was successively dropped over about 10 minutes with a Pasteur pipette (1 ml). After the dropping, the reaction was completed by stirring at 130 to 137 ° C. for about 10 minutes. As a result of analyzing the reaction solution by gas chromatography, 99.3% was 4C2TFBAD. The obtained product was subjected to simple distillation to obtain 38.8 g of 4C2TFBAD having a purity of 99.8% (yield: 99.5%) as a fraction of 65 to 72 ° C./20 mmHg. The 4C2TFBAD residue containing iron chloride was 4.9 g.
［実施例２３～３１］
実施例２２で得られた塩化鉄を含む４Ｃ２ＴＦＢＡＤ残渣に新たに４Ｃ２ＴＦＢＡＣを５０ｇ仕込んで、実施例２２と同じ試験を行った。反応温度、純水の添加時間、添加水量と４Ｃ２ＴＦＢＡＤの収量を表３に示した（実施例２３）。さらに、同じ試験を繰り返し（実施例２４～３１）そのときの諸元を表３に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
[Examples 23 to 31]
The same test as in Example 22 was performed by newly charging 50 g of 4C2TFBAC into the 4C2TFBAD residue containing iron chloride obtained in Example 22. The reaction temperature, the addition time of pure water, the amount of added water and the yield of 4C2TFBAD are shown in Table 3 (Example 23). Further, the same test was repeated (Examples 24 to 31). Table 3 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
実施例２２で得られた塩化鉄を含む４Ｃ２ＴＦＢＡＤ残渣に新たに４Ｃ２ＴＦＢＡＣを５０ｇ仕込んで、実施例２２と同じ試験を行った。反応温度、純水の添加時間、添加水量と４Ｃ２ＴＦＢＡＤの収量を表３に示した（実施例２３）。さらに、同じ試験を繰り返し（実施例２４～３１）そのときの諸元を表３に示した。これらの試験中、無水・塩化第二鉄は追加しなかった。
The same test as in Example 22 was performed by newly charging 50 g of 4C2TFBAC into the 4C2TFBAD residue containing iron chloride obtained in Example 22. The reaction temperature, the addition time of pure water, the amount of added water and the yield of 4C2TFBAD are shown in Table 3 (Example 23). Further, the same test was repeated (Examples 24 to 31). Table 3 shows the specifications at that time. During these tests, no anhydrous ferric chloride was added.
上述の通り、本発明によれば、トリフルオロメチル基が置換したジハロメチル基置換芳香族化合物から目的とする芳香族アルデヒドを高い選択率かつ著しく短時間で得ることができる。
As described above, according to the present invention, the desired aromatic aldehyde can be obtained from the dihalomethyl group-substituted aromatic compound substituted with a trifluoromethyl group in a very short time with high selectivity.
以上、本発明の実施形態について説明したが、本発明は上記実施形態に限定されるものではなく、本発明の趣旨を逸脱しない範囲で、当業者の通常の知識に基づいて、以下の実施形態に対し適宜変更、改良可能であることはいうまでもない。
As mentioned above, although embodiment of this invention was described, this invention is not limited to the said embodiment, Based on the normal knowledge of those skilled in the art in the range which does not deviate from the meaning of this invention, following embodiment Needless to say, it can be appropriately changed and improved.
Claims (3)
- 一般式（１）で表されるジハロメチル基置換芳香族化合物を鉄塩の存在下に加水分解して一般式（２）で表されるホルミル基置換芳香族化合物を製造する方法であって、加水分解反応が生じる前にアルデヒド化合物と鉄塩を前記ジハロメチル基置換芳香族化合物に溶解することと、加水分解反応が起こるのに十分な反応温度に達した後に水をその消失速度を超えない速度で反応系内へ添加することを含む、前記ホルミル基置換芳香族化合物の製造方法。
- アルデヒド化合物が、該製造方法で得ようとするホルミル基置換芳香族化合物である、請求項１に記載のホルミル基置換芳香族化合物の製造方法。 The method for producing a formyl group-substituted aromatic compound according to claim 1, wherein the aldehyde compound is a formyl group-substituted aromatic compound to be obtained by the production method.
- アルデヒド化合物が、一般式（３）で表わされるアルデヒド化合物である、請求項１に記載のホルミル基置換芳香族化合物の製造方法。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102516047A (en) * | 2011-12-13 | 2012-06-27 | 联化科技股份有限公司 | Preparation methods of 2-(trifluoromethyl)benzaldehyde and intermediate thereof |
| CN106278837A (en) * | 2015-05-28 | 2017-01-04 | 联化科技（台州）有限公司 | The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde |
| WO2019052440A1 (en) | 2017-09-12 | 2019-03-21 | 江苏恒瑞医药股份有限公司 | Deuterium atom-substituted indole formamide derivative, preparation method therefor, and medical applications thereof |
| CN111348996A (en) * | 2018-12-24 | 2020-06-30 | 江苏联化科技有限公司 | 2-benzoyl malonate compound, preparation method and application thereof |
| WO2020132792A1 (en) * | 2018-12-24 | 2020-07-02 | 江苏联化科技有限公司 | 2-benzoyl malonate compound, preparation method therefor and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0077853A1 (en) * | 1980-10-10 | 1983-05-04 | Occidental Chemical Corporation | Novel trifluoromethyl benzal chlorides and process for the preparation thereof |
| JPH0748307A (en) * | 1992-11-26 | 1995-02-21 | Hoechst Ag | Preparation of aromatic aldehyde |
| JP2005272324A (en) * | 2004-03-23 | 2005-10-06 | Central Glass Co Ltd | 3-formyl-5-trifluoromethylbenzonitrile derivative and its manufacturing method |
| JP2006045095A (en) * | 2004-08-03 | 2006-02-16 | Central Glass Co Ltd | 3-formyl-5-trifluoromethylbenzonitrile derivative and method for producing the same |
| JP2006160635A (en) * | 2004-12-03 | 2006-06-22 | Central Glass Co Ltd | Method for producing 2-trifluoromethyl-5-fluorobenzaldehyde and its derivative |
| JP2006213630A (en) * | 2005-02-03 | 2006-08-17 | Central Glass Co Ltd | Method for producing 2-trifluoromethyl-6-fluorobenzaldehyde and its derivative |
-
2009
- 2009-08-18 JP JP2009189346A patent/JP2011037803A/en active Pending
-
2010
- 2010-07-30 WO PCT/JP2010/062879 patent/WO2011021492A1/en active Application Filing
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0077853A1 (en) * | 1980-10-10 | 1983-05-04 | Occidental Chemical Corporation | Novel trifluoromethyl benzal chlorides and process for the preparation thereof |
| JPH0748307A (en) * | 1992-11-26 | 1995-02-21 | Hoechst Ag | Preparation of aromatic aldehyde |
| JP2005272324A (en) * | 2004-03-23 | 2005-10-06 | Central Glass Co Ltd | 3-formyl-5-trifluoromethylbenzonitrile derivative and its manufacturing method |
| JP2006045095A (en) * | 2004-08-03 | 2006-02-16 | Central Glass Co Ltd | 3-formyl-5-trifluoromethylbenzonitrile derivative and method for producing the same |
| JP2006160635A (en) * | 2004-12-03 | 2006-06-22 | Central Glass Co Ltd | Method for producing 2-trifluoromethyl-5-fluorobenzaldehyde and its derivative |
| JP2006213630A (en) * | 2005-02-03 | 2006-08-17 | Central Glass Co Ltd | Method for producing 2-trifluoromethyl-6-fluorobenzaldehyde and its derivative |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102516047A (en) * | 2011-12-13 | 2012-06-27 | 联化科技股份有限公司 | Preparation methods of 2-(trifluoromethyl)benzaldehyde and intermediate thereof |
| CN102516047B (en) * | 2011-12-13 | 2013-11-06 | 联化科技股份有限公司 | Preparation methods of 2-(trifluoromethyl)benzaldehyde and intermediate thereof |
| CN106278837A (en) * | 2015-05-28 | 2017-01-04 | 联化科技（台州）有限公司 | The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde |
| WO2019052440A1 (en) | 2017-09-12 | 2019-03-21 | 江苏恒瑞医药股份有限公司 | Deuterium atom-substituted indole formamide derivative, preparation method therefor, and medical applications thereof |
| CN111348996A (en) * | 2018-12-24 | 2020-06-30 | 江苏联化科技有限公司 | 2-benzoyl malonate compound, preparation method and application thereof |
| WO2020132792A1 (en) * | 2018-12-24 | 2020-07-02 | 江苏联化科技有限公司 | 2-benzoyl malonate compound, preparation method therefor and application thereof |
| CN111348996B (en) * | 2018-12-24 | 2023-09-08 | 江苏联化科技有限公司 | 2-benzoyl malonate compound, and preparation method and application thereof |
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